title: Human enterovirus species B in ileocecal Crohn's disease.
abstract: OBJECTIVE
  Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency of NOD2 mutations. Recent findings implicate a role of NOD2 and another CD susceptibility gene, ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD.
  
  
  METHODS
  We used immunohistochemistry and in situ hybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis.
  
  
  RESULTS
  All patients with ICD had disease-associated polymorphisms in NOD2 or ATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia.
  
  
  CONCLUSIONS
  The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Nyström
authors.forename: Tove
authors.initials: T
authors.lastname: Berg
authors.forename: Elin
authors.initials: E
authors.lastname: Lundin
authors.forename: Oskar
authors.initials: O
authors.lastname: Skog
authors.forename: Inga
authors.initials: I
authors.lastname: Hansson
authors.forename: Gun
authors.initials: G
authors.lastname: Frisk
authors.forename: Ivana
authors.initials: I
authors.lastname: Juko-Pecirep
authors.forename: Mats
authors.initials: M
authors.lastname: Nilsson
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
authors.forename: Yigael
authors.initials: Y
authors.lastname: Finkel
authors.forename: Jonas
authors.initials: J
authors.lastname: Fuxe
authors.forename: Alkwin
authors.initials: A
authors.lastname: Wanders